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  • 1
    ISSN: 1432-0584
    Keywords: Key words Complement system ; C1 inhibitor ; Bone marrow transplantation ; Capillary leak syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Capillary leak syndrome (CLS) is a severe complication after bone marrow transplantation (BMT). To investigate whether there is a pathogenetic role of the complement system, we monitored the levels of the terminal complement complex C5b-9 (TCC) and C3a-desArg as indicators of an activation of the complement system and the inhibitor of the classical pathway of the complement cascade, C1 inhibitor (C1-INH), in 48 bone marrow transplant recipients from 1 week before to 5 weeks after transplantation. Capillary leak syndrome developed in 7 out of 48 patients between days 1 and 12 after BMT. Complement activation as indicated by TCC levels was more pronounced in patients with CLS (n = 7) from day –8 to +28 (p〈0.05; day –1) and the elevation of TCC levels lasted longer in CLS patients (peak day 21) than in patients without this complication (peak day 7). Mean C3a-desArg levels were highest in patients with CLS reaching a peak at day 7. During the early posttransplant period a significant elevation of C1-INH levels (p〈0.01 and p〈0.05 respectively) compared with baseline levels (day –8) was found in patients with and without CLS, which was more pronounced in those patients with CLS (p〈0.05). Although we could not observe an absolute C1-INH deficiency as compared to healthy individuals our data support the presence of a relative deficiency of the inhibitor which might explain the reported beneficial effects of C1-INH substitution in BMT related CLS.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Complement system ; C1 inhibitor ; Bone marrow transplantation ; Capillary leak syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Capillary leak syndrome (CLS) is a severe complication after bone marrow transplantation (BMT). To investigate whether there is a pathogenetic role of the complement system, we monitored the levels of the terminal complement complex C5b-9 (TCC) and C3a-desArg as indicators of an activation of the complement system and the inhibitor of the classical pathway of the complement cascade, C1 inhibitor (C1-INH), in 48 bone marrow transplant recipients from 1 week before to 5 weeks after transplantation. Capillary leak syndrome developed in 7 out of 48 patients between days 1 and 12 after BMT. Complement activation as indicated by TCC levels was more pronounced in patients with CLS (n=7) from day −8 to +28 (p〈0.05; day −1) and the elevation of TCC levels lasted longer in CLS patients (peak day 21) than in patients without this complication (peak day 7). Mean C3a-desArg levels were highest in patients with CLS reaching a peak at day 7. During the early posttransplant period a significant elevation of C1-INH levels (p〈0.01 and p〈0.05 respectively) compared with baseline levels (day −8) was found in patients with and without CLS, which was more pronounced in those patients with CLS (p〈0.05). Although we could not observe an absolute C1-INH deficiency as compared to healthy individuals our data support the presence of a relative deficiency of the inhibitor which might explain the reported beneficial effects of C1-INH substitution in BMT related CLS.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Interleukin-12 ; non-obese diabetic mice ; cyclophosphamide ; T-helper type 1/2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A single dose of cyclophosphamide (250 mg/kg) is known to synchronize and accelerate development of diabetes in non-obese diabetic mice. We have reported previously that cyclophosphamide treatment of 10-week-old female non-obese diabetic mice induces a shift from T-helper type 2 to T-helper type 1 activity in islet lesions. We now show that this shift in regulatory T-cell function is preceded by the expression of interleukin-12 in the islets as well as in the spleen. In the spleen macrophages were identified as the interleukin-12 expressing cell type. At the same time there was little induction of tumour necrosis factor alpha gene expression by macrophages. Since interleukin-12 is well known to drive T-helper cell type 1 responses we assume that interleukin-12 released by macrophages mediates the accelerating effect of cyclophosphamide on islet inflammation in non-obese diabetic mice. mRNA expression of the p40 chain of interleukin-12 in response to cyclophosphamide was not seen in macrophages of Balb/c mice and thus represents an immune abnormality of non-obese diabetic mice favouring T-helper type 1 reactions.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Key words Inducible NO synthase ; NOD mice ; cyclophosphamide ; T-helper cell type 1 ; T-helper cell type 2.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In pancreatic lesions of non-obese diabetic (NOD) mice the expression of inducible nitric oxide synthase (iNOS) and of the cytokines interferon-gamma and interleukin-4 were studied. Strong iNOS expression as determined at the level of transcription, translation and of enzyme activity was associated with destructive insulitis as seen 8–10 days after cyclophosphamide treatment of 70- to 80-day-old female NOD mice. Immunohistochemistry showed iNOS associated with infiltrating macrophages but not in endocrine cells. The enhancement of iNOS after cyclophosphamide correlated with an increase of T-helper type 1 (Th1) associated interferon-gamma expression while T-helper type 2 (Th2) associated interleukin-4 was the dominant cytokine prior to cyclophosphamide and after diabetes onset. We conclude that insulitis in young NOD mice is carried by Th2 cells while cyclophosphamide enhanced insulitis is determined by Th1 cells. Macrophages show two different functional states in insulitis; strong iNOS expression in macrophages is associated with destructive insulitis. [Diabetologia (1994) 37: 1154–1158]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Inducible NO synthase ; NOD mice ; cyclophosphamide ; T-helper cell type 1 ; T-helper cell type 2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In pancreatic lesions of non-obese diabetic (NOD) mice the expression of inducible nitric oxide synthase (iNOS) and of the cytokines interferongamma and interleukin-4 were studied. Strong iNOS expression as determined at the level of transcription, translation and of enzyme activity was associated with destructive insulitis as seen 8–10 days after cyclophosphamide treatment of 70- to 80-day-old female NOD mice. Immunohistochemistry showed iNOS associated with infiltrating macrophages but not in endocrine cells. The enhancement of iNOS after cyclophosphamide correlated with an increase of T-helper type 1 (Th1) associated interferon-gamma expression while T-helper type 2 (Th2) associated interleukin-4 was the dominant cytokine prior to cyclophosphamide and after diabetes onset. We conclude that insulitis in young NOD mice is carried by Th2 cells while cyclophosphamide enhanced insulitis is determined by Th1 cells. Macrophages show two different functional states in insulitis; strong iNOS expression in macrophages is associated with destructive insulitis.
    Type of Medium: Electronic Resource
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